Protocatechuic acid improves functional recovery after spinal cord injury by attenuating blood-spinal cord barrier disruption and hemorrhage in rats

Park, Chan Sol; Lee, Jee Youn; Choi, Hae Young; Ju, Bong Gun; Youn, Inchan; Yune, Tae Young

doi:10.1016/j.neuint.2019.01.013

Cited by 27 publications

(15 citation statements)

References 52 publications

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“…The structure of the platelet GP Ib is more stable, which prevents the change to platelet GPIb structure caused by high shear stress. In addition, in recent years, an increasing number of protective effects of protocatechuic acid on the body, such as the effect of intracranial hemorrhage in mice 38 and of the blood-spinal barrier hemorrhage in rats 43 , have been identi ed. However, how to inhibit this process remains to be studied.…”

Section: Discussionmentioning

confidence: 99%

Inhibitory Effect of Protocatechuic Acid on Platelet Aggregation Induced by High Shear Stress

Dan

et al. 2020

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Background Platelet aggregation helps stop bleeding and thrombosis and blocks atherosclerosis, a cause of heart and cerebrovascular disease. Presently, bleeding and drug resistance are the most common side effects of clinically used antiplatelet drugsthus, it is particularly important to identify new antiplatelet drugs that can avoid or reduce these side effects. Method In this study,we used microfluidic chips in vitro to simulate the highly narrow bionic blood vessels of atherosclerosis to investigate the platelet aggregation on shear force-induced drug inhibition. Use flow cytometry to detect platelet activation markers（CD62P）.And thromboelasmograph and automatic coagulation analyzer were used to detect the coagulation function of blood after the action of protocatechuic acid. Results we found that platelets strongly aggregated after passing through the highly narrow microfluidic channel, and the aggregation can be inhibited by protocatechuic acid and CD42b but not by aspirin, tirofiban and other drugs.and protocatechuic acid inhibits platelet aggregation mainly by inhibiting interactions between platelet glycoprotein 1b (GPIb) and von Willebrand factor (vWF)，but does not activate platelets（ did not increase the expression of CD62P, a platelet activation marker）.In addition, protocatechuic acid did not significantly inhibit platelet aggregation induced by other endogenous agonists, such as collagen and ADP.It was found that the inhibitory effect of protocatechuic acid on platelet aggregation did not affect blood production, coagulation time, or coagulation function, reducing the drug resistance and frequent bleeding caused by aspirin. Conclusion Protocatechuic acid could selectively inhibit high shear force-induced platelet aggregation without affecting blood clotting function, However, the effect of the combination of the Protocatechuic acid and aspirin or other drugs remains to be studied. Therefore, we will conduct further studies on protocatechuic acid for new antithrombotic drugs, which can prevent thrombosis without affecting clotting time.

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Section: Discussionmentioning

confidence: 99%

Inhibitory Effect of Protocatechuic Acid on Platelet Aggregation Induced by High Shear Stress

Dan

et al. 2020

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“…Previous studies have mainly focused on drug treatment after SCI [14,15]. However, this often has certain side effects, affecting the quality of life of patients.…”

Section: Introductionmentioning

confidence: 99%

Underwater-treadmill training attenuates blood-spinal cord barrier disruption by promoting angiogenesis and inhibiting MMP-2/9 expression following spinal cord injury

Ying¹,

Xie²,

Li³

et al. 2020

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Background The blood-spinal cord barrier (BSCB) can be seriously damaged after SCI and is considered to be a therapeutic target. Exercise training is a recognized method for the treatment of SCI. The destruction of the BSCB mediated by matrix metalloproteinase (MMP) leads to inflammation, neurotoxin production, and apoptosis of neurons. The failure of effective regeneration of new blood vessels is also an important reason for the difficulty of recovery after SCI. We introduced underwater-treadmill training (TT) for the first time, which can help SCI rats successfully exercise, and we explored the role of TT in promoting the ability to exercise after SCI and its possible mechanism. Methods SCI models were established and randomly divided into three groups. Rats underwent TT after SCI. The degree of neurological deficit, water content, BSCB permeability, protein expression and ultrastructure of vascular endothelial cells were assessed by the BBB motor rating scale, haematoxylin-eosin (HE) staining, Evans blue (EB) staining, Western blot (WB) experiments, and immunofluorescence and transmission electron microscopy (TEM). Results Our experiments show that TT reduces the permeability of BSCB and decreased tissue structure damage and improved functional recovery after SCI; TT prevent the loss of TJ and AJ protein; TT promotes angiogenesis and inhibits the expression of MMP-2 and MMP-9 after SCI. Conclusions In this study, the results indicate that TT promotes functional recovery partly for the following reasons: (1) TT protects residual BSCB structure from further damage; (2) it promotes vascular regeneration; and (3) it inhibits the expression of MMP-2/9 to mitigate BSCB damage.

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“…Previous studies have mainly focused on drug treatment after SCI [18,19]. However, this often has certain side effects, affecting the quality of life of patients.…”

Section: Introductionmentioning

confidence: 99%

Water treadmill training attenuates blood-spinal cord barrier disruption by promoting angiogenesis and inhibiting MMP-2/9 expression following spinal cord injury

Ying

Xie

et al. 2020

Preprint

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Background: The permeability of blood-spinal cord barrier (BSCB) is mainly determined by the junction complex of adjacent endothelial cells, including tight junction (TJ) and adhesion junction (AJ), which can be severely damaged after spinal cord injury (SCI). Exercise training is a recognized method for the treatment of SCI. The destruction of the BSCB mediated by matrix metalloproteinase (MMP) leads to inflammation, neurotoxin production, and apoptosis of neurons. The failure of effective regeneration of new blood vessels is also an important reason for the difficulty of recovery after SCI. We introduced water treadmill training (TT) for the first time, which can help SCI rats successfully exercise, and we explored the role of TT in promoting the ability to exercise after SCI and its possible mechanism.Methods: Sprague-Dawley (200–250g) rats were randomly divided into three groups. SCI models were established and rats underwent TT after SCI. Animals were sacrificed 7 d or 14 d post-surgery. The degree of neurological deficit, water content, BSCB permeability, apoptosis, protein expression and ultrastructure of vascular endothelial cells (EC) were assessed by the Basso-Beattie-Bresnahan (BBB) motor rating scale, haematoxylin-eosin (HE) staining, Evans blue (EB) staining, TUNEL staining, Western blot (WB) experiments, and immunofluorescence and transmission electron microscopy (TEM). Results: Our experiments show that TT reduces the permeability of BSCB and decreased tissue structure damage. TT improved functional recovery and it has significant significance when compared with the M group after SCI; TJ and AJ proteins increased significantly after TT training in SCI rats. TT training reduced apoptosis induced by SCI. TT can promote angiogenesis and the expressions of MMP-2 and MMP-9 were significantly inhabited by TT after SCI.Conclusions: In this study, the results indicate that TT promotes functional recovery partly for the following reasons: (1) TT protects residual BSCB structure from further damage; (2) it promotes vascular regeneration; and (3) it inhibits the expression of MMP-2/9 to mitigate BSCB damage.

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Protocatechuic acid improves functional recovery after spinal cord injury by attenuating blood-spinal cord barrier disruption and hemorrhage in rats

Cited by 27 publications

References 52 publications

Inhibitory Effect of Protocatechuic Acid on Platelet Aggregation Induced by High Shear Stress

Inhibitory Effect of Protocatechuic Acid on Platelet Aggregation Induced by High Shear Stress

Underwater-treadmill training attenuates blood-spinal cord barrier disruption by promoting angiogenesis and inhibiting MMP-2/9 expression following spinal cord injury

Water treadmill training attenuates blood-spinal cord barrier disruption by promoting angiogenesis and inhibiting MMP-2/9 expression following spinal cord injury

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